mIRN21

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MIR21
Identifiers
Aliases MIR21, MIRN21, hsa-mir-21, miR-21, miRNA21, microRNA 21
External IDs GeneCards: MIR21
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC) Chr 17: 59.84 – 59.84 Mb n/a
PubMed search [1] n/a
Wikidata
View/Edit Human

microRNA 21 also known as hsa-mir-21 or miRNA21 is a mammalian microRNA that is encoded by the MIR21 gene.[2]

MIRN21 was one of the first mammalian microRNAs identified. The mature miR-21 sequence is strongly conserved throughout evolution. The human microRNA-21 gene is located on plus strand of chromosome 17q23.2 (55273409–55273480) within a coding gene TMEM49 (also called vacuole membrane protein). Despite being located in intronic regions of a coding gene in the direction of transcription, it has its own promoter regions and forms a ~3433-nt long primary transcript of miR-21 (known as pri-miR-21) which is independently transcribed. The stem–loop precursor of miR-21(pre-miR-21) resides between nucleotides 2445 and 2516 of pri-miR-21.

Mature miR-21[edit]

Pri-miR-21 is cut by the endonuclease Drosha in the nucleus to produce pre-miR-21, which is exported into the cytosol. This pre-miR-21 is then cut into a short RNA duplex by Dicer in the cytosol. Although abundance of both strands is equal by transcription, only one strand (miR-21) is selected for processing as mature microRNA based on the thermodynamic stability of each end of the duplex, while the other strand (designated with an asterisk; miR-21*) is generally degraded. Mature microRNA is then loaded into microRNA ribonucleoprotein complex RISC (RNA-induced silencing complex) and guided to target mRNAs with near perfect complimentarily at 3’UTR.

Targets[edit]

A number of targets for microRNA-21 have been experimentally validated and most of them are tumor suppressors, Notable targets include:

Clinical significance[edit]

Cancer[edit]

miR-21 is one of the most frequently upregulated miRNAs in solid tumours, and its high levels were first described in B cell lymphomas. Overall, miR-21 is considered to be a typical 'onco-miR', which acts by inhibiting the expression of phosphatases, which limit the activity of signalling pathways such as AKT and MAPK.[19] miR-21 can be transcriptionally activated by NF-κB and downregulate phosphatases PDCD4 and PTEN. A recent study also suggested that miR-21 could provide a link between inflammation and cancer.[19] As most of the targets of miR-21 are tumor suppressors, miR-21 is associated with a wide variety of cancers including that of breast,[20] ovaries,[21] cervix,[22] colon,[11] lung,[23] liver,[12] brain,[24] esophagus,[25] prostate,[23] pancreas,[23] and thyroid.[26] A 2014 meta-analysis of 36 studies evaluated circulating miR-21 as a biomarker of various carinomas, finding it has potential as a tool for early diagnosis.[27]

Cardiac disease[edit]

miR-21 has been shown to play important role in development of heart disease. It is one of the microRNAs whose expression is increased in failing murine and human hearts.[17][28] Further, inhibition of microRNAs in mice using chemically modified and cholesterol-conjugated miRNA inhibitors (antagomirs) was shown to inhibit interstitial fibrosis and improve cardiac function in a pressure- overload cardiac disease mice model.[17] Surprisingly, miR-21 global knock-out mice did not show any overt phenotype when compared with wild type mice with respect to cardiac stress response. Similarly, short (8-nt) oligonucleotides designed to inhibit miR-21 could not inhibit cardiac hypertrophy or fibrosis.[29] In another study with a mouse model of acute myocardial infarction, miR-21 expression was found to be significantly lower in infarcted areas and overexpression of miR-21 in those mice via adenovirus-mediated gene transfer decreased myocardial infarct size.[30] miR-21 has been hypothesized to be an intermediary in the effects of air pollution that lead to endothelial dysfunction and eventually to cardiac disease. Expression of miR-21 is negatively associated with exposure to PM10 air pollution and may mediate its effect on small blood vessels.[31]

References[edit]

  1. ^ "Human PubMed Reference:". 
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  5. ^ Zheng J, Xue H, Wang T, Jiang Y, Liu B, Li J, Liu Y, Wang W, Zhang B, Sun M (Mar 2011). "miR-21 downregulates the tumor suppressor P12 CDK2AP1 and stimulates cell proliferation and invasion". Journal of Cellular Biochemistry. 112 (3): 872–80. doi:10.1002/jcb.22995. PMID 21328460. 
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  7. ^ Lu TX, Munitz A, Rothenberg ME (Apr 2009). "MicroRNA-21 is up-regulated in allergic airway inflammation and regulates IL-12p35 expression". Journal of Immunology. 182 (8): 4994–5002. doi:10.4049/jimmunol.0803560. PMC 4280862Freely accessible. PMID 19342679. 
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  11. ^ a b Asangani IA, Rasheed SA, Nikolova DA, Leupold JH, Colburn NH, Post S, Allgayer H (Apr 2008). "MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer". Oncogene. 27 (15): 2128–36. doi:10.1038/sj.onc.1210856. PMID 17968323. 
  12. ^ a b Meng F, Henson R, Wehbe-Janek H, Ghoshal K, Jacob ST, Patel T (Aug 2007). "MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer". Gastroenterology. 133 (2): 647–58. doi:10.1053/j.gastro.2007.05.022. PMC 4285346Freely accessible. PMID 17681183. 
  13. ^ Gabriely G, Wurdinger T, Kesari S, Esau CC, Burchard J, Linsley PS, Krichevsky AM (Sep 2008). "MicroRNA 21 promotes glioma invasion by targeting matrix metalloproteinase regulators". Molecular and Cellular Biology. 28 (17): 5369–80. doi:10.1128/MCB.00479-08. PMC 2519720Freely accessible. PMID 18591254. 
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  15. ^ Schramedei K, Mörbt N, Pfeifer G, Läuter J, Rosolowski M, Tomm JM, von Bergen M, Horn F, Brocke-Heidrich K (Jun 2011). "MicroRNA-21 targets tumor suppressor genes ANP32A and SMARCA4". Oncogene. 30 (26): 2975–85. doi:10.1038/onc.2011.15. PMC 3134876Freely accessible. PMID 21317927. 
  16. ^ Kim YJ, Hwang SJ, Bae YC, Jung JS (Dec 2009). "MiR-21 regulates adipogenic differentiation through the modulation of TGF-beta signaling in mesenchymal stem cells derived from human adipose tissue". Stem Cells. 27 (12): 3093–102. doi:10.1002/stem.235. PMID 19816956. 
  17. ^ a b c Thum T, Gross C, Fiedler J, Fischer T, Kissler S, Bussen M, Galuppo P, Just S, Rottbauer W, Frantz S, Castoldi M, Soutschek J, Koteliansky V, Rosenwald A, Basson MA, Licht JD, Pena JT, Rouhanifard SH, Muckenthaler MU, Tuschl T, Martin GR, Bauersachs J, Engelhardt S (Dec 2008). "MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts". Nature. 456 (7224): 980–4. doi:10.1038/nature07511. PMID 19043405. 
  18. ^ Sayed D, Rane S, Lypowy J, He M, Chen IY, Vashistha H, Yan L, Malhotra A, Vatner D, Abdellatif M (Aug 2008). "MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths". Molecular Biology of the Cell. 19 (8): 3272–82. doi:10.1091/mbc.E08-02-0159. PMC 2488276Freely accessible. PMID 18508928. 
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  27. ^ Wu K, Li L, Li S (Mar 2015). "Circulating microRNA-21 as a biomarker for the detection of various carcinomas: an updated meta-analysis based on 36 studies". Tumour Biology. 36 (3): 1973–81. doi:10.1007/s13277-014-2803-2. PMID 25527152. 
  28. ^ Roy S, Khanna S, Hussain SR, Biswas S, Azad A, Rink C, Gnyawali S, Shilo S, Nuovo GJ, Sen CK (Apr 2009). "MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue". Cardiovascular Research. 82 (1): 21–9. doi:10.1093/cvr/cvp015. PMC 2652741Freely accessible. PMID 19147652. 
  29. ^ Patrick DM, Montgomery RL, Qi X, Obad S, Kauppinen S, Hill JA, van Rooij E, Olson EN (Nov 2010). "Stress-dependent cardiac remodeling occurs in the absence of microRNA-21 in mice". The Journal of Clinical Investigation. 120 (11): 3912–6. doi:10.1172/JCI43604. PMC 2964990Freely accessible. PMID 20978354. 
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  31. ^ Louwies T, Vuegen C, Panis LI, Cox B, Vrijens K, Nawrot TS, De Boever P (2016). "miRNA expression profiles and retinal blood vessel calibers are associated with short-term particulate matter air pollution exposure". Environmental Research. 147: 24–31. doi:10.1016/j.envres.2016.01.027. PMID 26836502. 

Further reading[edit]

  • Cardin S, Guasch E, Luo X, Naud P, Le Quang K, Shi Y, Tardif JC, Comtois P, Nattel S (Oct 2012). "Role for MicroRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure". Circulation. Arrhythmia and Electrophysiology. 5 (5): 1027–35. doi:10.1161/CIRCEP.112.973214. PMID 22923342. 
  • Zhong Z, Dong Z, Yang L, Gong Z (Oct 2012). "miR-21 induces cell cycle at S phase and modulates cell proliferation by down-regulating hMSH2 in lung cancer". Journal of Cancer Research and Clinical Oncology. 138 (10): 1781–8. doi:10.1007/s00432-012-1287-y. PMID 22806311. 

External links[edit]